Methods of aiding in the diagnosis of prostate cancer

Abstract

The current invention provides a method for aiding in the assessment of prostate cancer (including metastatic prostate cancer) and/or benign prostate hyperplasia in a patient, wherein the method comprises the step of determining the level of Glycine N-methyltransferase (GNMT) nucleic acid and/or protein in a sample from the patient. The invention also provides compounds that target Glycine N-methyltransferase (GNMT) protein and/or nucleic acid for use in treating prostate cancer. Also provided are screening methods for selecting a compound considered to be useful in treating prostate cancer, comprising the steps of determining the ability of a test compound to reduce GNMT activity and selecting a compound that reduces GNMT activity. The invention also provides methods for aiding in the diagnosis of prostate cancer in a patient comprising obtaining a sample from the patient and assessing said sample for a marker of GNMT activity.

1 . A method for aiding in the assessment of prostate cancer (including metastatic prostate cancer) and/or benign prostate hyperplasia in a patient, wherein the method comprises the step of determining the level of Glycine N-methyltransferase (GNMT) nucleic acid and/or protein in a sample from the patient. 
     
     
         2 . The method of  claim 1  wherein the patient is; (i) at risk of developing prostate cancer; or (ii) has already been diagnosed with prostate cancer; or (iii) has undergone treatment for prostate cancer. 
     
     
         3 . The method of  claim 1  wherein the sample is a blood sample, a urine sample, a prostate massage urine sample, a lymph sample or a sample of seminal fluid. 
     
     
         4 . The method of  claim 1 , wherein the method is for assessing the likely progression of prostate cancer in the patient. 
     
     
         5 . The method of  claim 1  wherein the method is for assessing and/or predicting the development of prostate cancer. 
     
     
         6 . The method of  claim 1 , wherein the method is for diagnosing prostate cancer in the patient. 
     
     
         7 . The method of  claim 1 , wherein the method is for assessing the response of the patient to treatment. 
     
     
         8 . The method of  claim 7  wherein the method is for assessing the likely progression of response of the patient to treatment. 
     
     
         9 . The method of  claim 1 , wherein the method is for choosing patients for treatment for prostate cancer. 
     
     
         10 . The method of  claim 1 , wherein the method is for monitoring response of patients to treatment or for monitoring relapse in patients. 
     
     
         11 . The method of  claim 1 , wherein the method is for assessing the progress of clinical trials. 
     
     
         12 . A method for assessing a prostate cancer (including metastatic prostate cancer) and/or benign prostate hyperplasia treatment regime, the method comprising the step of determining the level of GNMT nucleic acid and/or protein in a sample from patients receiving the treatment regime. 
     
     
         13 - 35 . (canceled) 
     
     
         36 . A screening method for selecting a drug-like compound or lead compound for the development of a drug-like compound considered to be useful in treating prostate cancer, comprising the steps of;
 determining the ability of a test compound to reduce GNMT activity; and   selecting a compound that reduces GNMT activity.   
     
     
         37 . The screening method of  claim 36  further comprising the steps of;
 determining the ability of the test compound to reduce SAH sensitive methyltransferase activity; and 
 selecting a compound that does not reduce SAH sensitive methyltransferase activity. 
 
     
     
         38 . The screening method of  claim 36  wherein the compound is selected if it has an IC50 value for GNMT of less than 1 mM, less than 1 μM or less than 1 nM. 
     
     
         39 . The screening method of  claim 36  wherein the effect of the test compound on the methylation of DNA is assessed. 
     
     
         40 . The screening method of  claim 36  wherein the effect of the test compound on the methylation of protein is assessed. 
     
     
         41 . The screening method of  claim 36  wherein the effect of the test compound on levels of free methionine and/or SAM in cells is assessed. 
     
     
         42 . The screening method of  claim 36  wherein the effect of the test compound on the tissue levels of SAH, methionine and/or SAM is assessed. 
     
     
         43 . The screening method of  claim 36  wherein the effect of the test compound on the ratio of SAM to SAH and/or sarcosine is assessed. 
     
     
         44 . The screening method of  claim 36  wherein the test compound is exposed to purified GNMT, or purified recombinant GNMT. 
     
     
         45 . The screening method of  claim 36  wherein the test compound is exposed to a cell expressing GNMT, or an extract of such a cell. 
     
     
         46 . The screening method of  claim 45  wherein the cell or cell extract has been exposed to androgen. 
     
     
         47 . The screening method of  claim 46  wherein the cell or cell extract has been exposed to testosterone, R1881, dihydrotestosterone (DHT) or mibolerone. 
     
     
         48 . The screening method of  claim 36  further comprising the step of assessing the effect of the test compound in combination with an androgen. 
     
     
         49 . The screening method of  claim 48  wherein the androgen is selected from, but not limited to, the group comprising testosterone, R1881, mibolerone or dihydrotestosterone. 
     
     
         50 . The screening method of  claim 48  wherein the androgen is testosterone or DHT. 
     
     
         51 . The screening method of  claim 45  wherein the cell or cell extract has been exposed to anti-androgen. 
     
     
         52 . The screening method of  claim 51 , wherein the anti-androgen is bicalutamide, cyproterone acetate or flutamide. 
     
     
         53 . The screening method of  claim 36  further comprising the step of determining the effect of the test compound on activation of androgen receptors in a cell or cell extract. 
     
     
         54 . The screening method of  claim 36  further comprising the step of determining the effect of the test compound on sarcosine, methionine, SAM and/or SAH levels in prostate cancer cells. 
     
     
         55 . The screening method of  claim 36  wherein the assay is performed over a timescale of less than 24 hours, preferably less than 72 hours, preferably less than 48 hours and more preferably over 24 hours or less. 
     
     
         56 - 64 . (canceled)